Muscleblind-like 2 (Mbnl2)-deficient mice as a model for myotonic dystrophy
Muscleblind-like 2 (Mbnl2)-deficient mice as a model for myotonic dystrophy
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DOI：
10.1002/dvdy.21428
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发表时间：
2008-02-01
影响因子：
2.5
通讯作者：
Chen, Fabian
中科院分区：
文献类型：
--
作者：
Hao, Minqi;Akrami, Kevan;Chen, Fabian
强直性肌营养不良（I）M）是最常见的成人发病型肌营养不良，由CTG或CCTG微卫星重复扩增引起。扩展的DM mRNA微卫星重复序列被认为在细胞核中积累，隔离肌盲蛋白，并干扰mRNA的选择性剪接。肌盲2（Mbnl 2）是已知结合CTG/CCTG RNA重复序列的肌盲RNA结合蛋白家族（也包括Mbnl 1和Mbnl 3）的成员。最近，研究表明Mbnl 1缺陷小鼠具有人DM的特征，包括肌强直和氯离子通道表达缺陷。在这里，我们证明了Mbnl 2缺陷小鼠也发生肌强直，并具有与人DM一致的骨骼肌病理学。我们还发现骨骼肌中氯离子通道（Clcn 1）的表达缺陷和mRNA剪接可能导致肌强直表型。我们的结果支持肌盲蛋白，特别是MBNL 2有助于人类DM发病机制的假设。
Myotonic dystrophy (I)M), the most common adult-onset muscular dystrophy, is caused by CTG or CCTG microsatellite repeat expansions. Expanded DM mRNA microsatellite repeats are thought to accumulate in the nucleus, sequester Muscleblind proteins, and interfere with alternative mRNA splicing. Muscleblind2 (Mbnl2) is a member of the family of Muscleblind RNA binding proteins (that also include Mbnl1 and Mbnl3) that are known to bind CTG/CCTG RNA repeats. Recently, it was demonstrated that Mbnl1-deficient mice have characteristic features of human DM, including myotonia and defective chloride channel expression. Here, we demonstrate that Mbnl2-deficient mice also develop myotonia and have skeletal muscle pathology consistent with human DM. We also find defective expression and mRNA splicing of the chloride channel (Clcn1) in skeletal muscle that likely contributes to the myotonia phenotype. Our results support the hypothesis that Muscleblind proteins and specifically MBNL2 contribute to the pathogenesis of human DM.